This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
Welcome!
Welcome to my website! It's an ongoing research adventure on the genetic basis of depression. I hope you find it interesting and informative. Please be aware that most tabs contain sub-tabs, but are also pages themselves (i.e. "gene", "protein", and "depression"). Feel free to contact me (top right corner) with any questions or suggestions!
What is Depression?
Major depression is a mental illness characterized by low mood and sadness for extended periods of time. These feelings may occur for no known reason [3]. It is more than just "feeling blue." Those affected experience interference with daily life, including their ability to work, eat, sleep, study, connect, and enjoy once-pleasurable activities [1]. Some common symptoms include:
|
|
Major depression is one of the most common mental disorders in the United States and affects 6.7% of the adult population each year [1]. However, depression is not distributed across genders and ethnic groups fairly. Women are 70% more likely to incur depression over the course of their lifetime than men, while non-hispanic white men are 40% more likely to experience depression than non-hispanic black men. The rate of depression among youth teenagers (aged 13-18) in the U.S. is 3.3%. The average age of onset is 32 years old [1]. Other factors that predict a tendency for developing depression include groups of people with less than a high school education, those previously married, those unable to work or who are unemployed, and those without medical insurance [2]. Almost 30% of substance abusers also struggle with major depression [3].
Additionally, 1 in 10 Americans report experiencing depression [2]. States with the highest percentage of adults affected with depression include West Virginia, Oklahoma, Arkansas, Louisiana, Mississippi, Tennessee, and Alabama (see Figure 1 [2]).
Additionally, 1 in 10 Americans report experiencing depression [2]. States with the highest percentage of adults affected with depression include West Virginia, Oklahoma, Arkansas, Louisiana, Mississippi, Tennessee, and Alabama (see Figure 1 [2]).
Figure 1. Age-standardized Percentage of Adults Meeting Criteria for Current Depression By State/Territory
What Causes Depression?
Depression is a complex disease that is attributable to a combination of genetic, biological, environmental, and psychological factors, including:
|
Researchers have noted differences in the brain scans of depressed and people who are not experiencing depression (see Figure 2 [4]). One difference includes a smaller hippocampus in those with depression [3]. It is unknown why people who experience depression tend to have a smaller hippocampus. One idea is that cortisol, a stress hormone, has a poisonous affect on the hippocampus. Cortisol is produced in excess in depressed people. Another idea is that people who experience depression are just naturally born with a smaller hippocampus [3].
|
Figure 2. PET scans of the brain showing differences of activity in individuals depressed and not depressed.
Serotonin (see Figure 3) is a "calming" neurotransmitter, a brain chemical that is involved with communication between the nerves, brain, and body [3]. A smaller hippocampus means less serotonin receptors. While some scientists believe that low levels of serotonin receptors contribute to depression, serotonin's role in depression remains unclear [5]. However, this molecule remains the target of many pharmaceutical drugs prescribed to treat depression.
|
Figure 3. The chemical structure of the neurotransmitter, serotonin.
|
Treatment
Pharamceuticals
Pharmaceuticals, called antidepressants, are sometimes prescribed to treat depression. The most common antidepressants work to prevent serotonin uptake (see image at right), increasing serotonin concentration in the brain [5]. The following SSRI's have been approved by the FDA:
|
However, research illuminates some flaws in antidepressants. A 2010 study shows that the magnitude of benefit from taking antidepressants increases with the severity of depression. Participants with severe depression saw relief in symptoms while those with mild depression were affected at the same rate as the placebo [7]. In fact, there are no peer-reviewed articles upholding the hypothesis that levels of serotonin in the brain contribute to depression [8]. New research cites the abnormal transmission of excitatory signals between brain cells as a contributing factor [5]. In a depressed brain, these signals don't go through, even though serotonin works to amplify them [5]. It is clear that more research needs to be done to find an effective drug to treat depression.
Psychotherapy
Cognitive-behavioral therapy (CBT) helps those with mental illness rewire their thinking patterns [9]. With the help of a therapist, the patient explores the relationship between their thoughts, feelings, and behaviors. The therapist aids with challenging irrational beliefs [9]. CBT assumes that a person's thought patterns affect their moods [11]. If dysfunctional thinking patterns are changed, mood changes too. It has two goals:
- cognitive restructuring
- behavioral activation (clients learn to overcome obstacles to participating in enjoyable activities) [11]
Alternative Therapies
Omega-3 Fatty Acids [12]
- The National Center for Complementary and Alternative Medicine (NCCAM) is currently sponsoring studies to investigate whether Omega-3 fatty acids affect symptoms of depression
- The FDA recognizes them as "generally safe"
- Studies contradict on the effectiveness of St. John's Wort, including some that show it is as effective as the placebo
- St. John's Wort interferes with many medications. For a full list, click here
- There is currently not enough research to evaluate the effectiveness of valerian
- It is safe over short periods of time (4-6 weeks)
- One meta analysis of 37 studies supports the general conclusion that it is effective
- It works in parallel to psychotherapy and physical therapy
- Relaxation techniques as more effective than no treatment at all, but less effective than CBT
- Research suggests that yoga is effective in treating symptoms of depression, but more research is necessary
Genetic Contributions
A recent study in twin pairs discovered a correlation between sleep duration and depression. Those twins with a longer sleep duration had fewer depressive symptoms. The heritability of depressive symptoms among those who sleep eight hours a night was 27% while those who only slept five hours a night had a heritability of 53%. Those sleeping for ten hours a night had a heritability of depressive symptoms of 49%. This study indicates a relation between circadian rhythms and depression and warrants for future research [16].
PER2, or "period circadian clock 2" is a gene recently associated with depression vulnerability [15]. A study on a Swedish population determined that PER2's genetic risk of depression did not require any major negative life events as a trigger. Another study found that a mutation in the PER2 gene lead to decreased expression of monoamine oxidase A (MAOA) and thus increased levels of dopamine in the ventral striatum of mice. The researchers believe that the resulting mood disorder-like behavior in mice was due to the elevated levels of dopamine [17]. For more on the PER2 gene, please see the "Gene" tab and its associated sub-tabs at the top of the page.
PER2, or "period circadian clock 2" is a gene recently associated with depression vulnerability [15]. A study on a Swedish population determined that PER2's genetic risk of depression did not require any major negative life events as a trigger. Another study found that a mutation in the PER2 gene lead to decreased expression of monoamine oxidase A (MAOA) and thus increased levels of dopamine in the ventral striatum of mice. The researchers believe that the resulting mood disorder-like behavior in mice was due to the elevated levels of dopamine [17]. For more on the PER2 gene, please see the "Gene" tab and its associated sub-tabs at the top of the page.
References
[1] National Institute of Mental Health
[2] CDC Data & Statistics
[3] WebMD. Causes of Depression. Retrieved January 27, 2014, from http://www.webmd.com/depression/guide/causes-depression
[4] WebMD. Depression Slideshow. Retrieved January 27, 2014, from http://www.webmd.com/depression/ss/slideshow-depression-overview
[5] (2013, March 18). Depression stems from miscommunication between brain cells; Study challenges role of serotonin in depression. Science Daily. Retrieved from sciencedaily.com
[6] Mayo Clinic. (2013). Selective serotonin reuptake inhibitors (SSRIs). Retrieved February 3, 2014, from http://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825
[7] Fournier, Jay C. et al. (2010). Antidepressant Drug Effects and Depression Severity: A Patient Level Meta-analysis. The Journal of the American Medical Association. 303(1), 47-53. doi: 10.1001/jama.2009.1943
[8] Lacasse, J.R., Leo, J. (2005). Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med 2(12): e392. doi:10.1371/journal.pmed.0020392
[9] NAMI. (2012). Cognitive Behavioral Therapy (CBT). http://www.nami.org/Template.cfmSection=About_Treatments_and_Supports&template=/ContentManagement/ContentDisplay.cfm&ContentID=7952
[10] Psychology Today. http://www.psychologytoday.com/articles/200707/how-fight-depression-and-anxiety
[11] WebMD. Depression Help Center. http://www.webmd.com/depression/guide/cognitive-behavioral-therapy-for-depression
[12] Depressions and Complementary Health Practices: What the Science Says. (2011, December). NCCAM Clinical Digest, online. http://nccam.nih.gov/health/providers/digest/depression-science.htm?nav=cd
[13] Moyer, C. A., Rounds, J., & Hannum, J.W. (2004). A Meta-Analysis of Massage Therapy Research. Psychological Bulletin, 130(1), 3-18.
doi: 10.1037/0033-2909.130.1.1
[14] Jorm, A.F., Morgan, A.J., & Hetrick, S.J. (2008). Relaxation for depression. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD007142. DOI: 10.1002/14651858.CD007142.pub2.
[15] Lavebratt, C., Sjöholm, L., Partonen, T., Schalling, M., & Forsell, Y. (2010). PER2 Variantion Is Associated With Depression Vulnerability. Am J Med Genet Part B 153B:570-581. doi: 10.1002/ajmg.b.31021
[16] Piper, L. (2014, February 17). Sleep duration impacts on genetic risks of depressive symptoms. medwire News. Retrieved from http://www.medwirenews.com/55/105355/Affective_disorders/Sleep_duration_impacts_on_genetic_risk_of_depressive_symptoms.html
[17] Hampp, G. et al. (2008). Regulation Monoamine Oxidase A by Circadian-Clock Components Implies Clock Influence on Mood. Current Biology 18(9), 678-683. doi: 10.1016/j.cub.2008.04.012
[1] National Institute of Mental Health
[2] CDC Data & Statistics
[3] WebMD. Causes of Depression. Retrieved January 27, 2014, from http://www.webmd.com/depression/guide/causes-depression
[4] WebMD. Depression Slideshow. Retrieved January 27, 2014, from http://www.webmd.com/depression/ss/slideshow-depression-overview
[5] (2013, March 18). Depression stems from miscommunication between brain cells; Study challenges role of serotonin in depression. Science Daily. Retrieved from sciencedaily.com
[6] Mayo Clinic. (2013). Selective serotonin reuptake inhibitors (SSRIs). Retrieved February 3, 2014, from http://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825
[7] Fournier, Jay C. et al. (2010). Antidepressant Drug Effects and Depression Severity: A Patient Level Meta-analysis. The Journal of the American Medical Association. 303(1), 47-53. doi: 10.1001/jama.2009.1943
[8] Lacasse, J.R., Leo, J. (2005). Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med 2(12): e392. doi:10.1371/journal.pmed.0020392
[9] NAMI. (2012). Cognitive Behavioral Therapy (CBT). http://www.nami.org/Template.cfmSection=About_Treatments_and_Supports&template=/ContentManagement/ContentDisplay.cfm&ContentID=7952
[10] Psychology Today. http://www.psychologytoday.com/articles/200707/how-fight-depression-and-anxiety
[11] WebMD. Depression Help Center. http://www.webmd.com/depression/guide/cognitive-behavioral-therapy-for-depression
[12] Depressions and Complementary Health Practices: What the Science Says. (2011, December). NCCAM Clinical Digest, online. http://nccam.nih.gov/health/providers/digest/depression-science.htm?nav=cd
[13] Moyer, C. A., Rounds, J., & Hannum, J.W. (2004). A Meta-Analysis of Massage Therapy Research. Psychological Bulletin, 130(1), 3-18.
doi: 10.1037/0033-2909.130.1.1
[14] Jorm, A.F., Morgan, A.J., & Hetrick, S.J. (2008). Relaxation for depression. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD007142. DOI: 10.1002/14651858.CD007142.pub2.
[15] Lavebratt, C., Sjöholm, L., Partonen, T., Schalling, M., & Forsell, Y. (2010). PER2 Variantion Is Associated With Depression Vulnerability. Am J Med Genet Part B 153B:570-581. doi: 10.1002/ajmg.b.31021
[16] Piper, L. (2014, February 17). Sleep duration impacts on genetic risks of depressive symptoms. medwire News. Retrieved from http://www.medwirenews.com/55/105355/Affective_disorders/Sleep_duration_impacts_on_genetic_risk_of_depressive_symptoms.html
[17] Hampp, G. et al. (2008). Regulation Monoamine Oxidase A by Circadian-Clock Components Implies Clock Influence on Mood. Current Biology 18(9), 678-683. doi: 10.1016/j.cub.2008.04.012